The Construction Of Sirolimus-loaded Hernia Mesh And Its Anti-adhesion Performance

Background:Abdominal hernia is a common disease in clinic.The use of patches makes tension-free hernia repair widely used in the inguinal hernia.And now for the abdominal incision hernia repair,the application of the patch is more universal.The introduction of minimally invasive surgery makes laparoscopic technology more popular,which makes laparoscopic hernia repair become a common method of hernia repair.Polypropylene patch is the material for hernia repair,it can make the leukocyte free access to the gap which may decrease the mesh infection rate with good tissue compatibility.However,in the laparoscopic intraperitoneal onlay mesh repair,the patch is connected to the peritoneal and abdominal organs directly,so the polypropylene patch is easy to produce a strong inflammatory response which may cause adhesion.In order to reduce the generation of intraperitoneal adhesions,various composite meshes based on polypropylene materials have been used widely.Sirolimus,a macrolide immunosuppressive agent,it can achieve the immunosuppressive effect and inflammation inhibition by blocking the lymphocytes and other cells from G1 to S phase of the process.Therefore,sirolimus is mainly used clinically after the liver and kidney transplantation or cardiovascular scaffold coating to avoid the occurrence of stent restenosis.Some scholars have been made anti-adhesive polypropylene patch with sirolimus by hydrogel impregnation method and in animal experiments the new mesh achieved good results,however,this method may affect the physical properties of the patch.Purpose:This study evaluated the manufacturing method and anti-adhesion properties of a new composite mesh,which was made from sirolimus(SRL)grafts on a poly(L-lactic acid)(PLLA)modified polypropylene(PP)hernia mesh.Methods:Native PP mesh was first treated in the argon plasma and then exposed to the air which can produce oxygen-containing groups.PLLA was grafted onto argon plasma-treated PP mesh through catalysis of stannous chloride.SRL was grafted onto the surface of PP-PLLA meshes using catalysis of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC)and 4-dimethylaminopyridine(DMAP)in a maleic anhydride(CH2Cl2)solvent.A total of 54 Sprague-Dawley female rats were randomly divided into three groups.Animals received either SRL-coated meshes,PP-PLLA meshes or native PP meshes to repair abdominal wall defects.All animals survived until the end of the experiment.At different intervals,six rats from each group were euthanized by a lethal dose of chloral hydrate.Adhesion area and tenacity were evaluated at 1 week,2 week and 4 week time intervals.Sections of the mesh with adjacent tissues were assessed histologically.Results:ATR-FTIR indicated the existence of a C=O group absorption peak(1724.1cm-1),and scanning electron microscope morphological analysis indicated that the surface of the PP mesh was covered with SRL.Compared to the native PP meshes and PP-PLLA meshes,SRL-coated meshes demonstrated the greatest ability to decrease the formation of adhesions(P<0.05)and inflammation.Conclusions:The SRL-coated composite mesh showed minimal formation of intra-abdominal adhesions in a rat model of abdominal wall defect repair.